A New Integrated Endoscope System Project Summary This proposal is a collaborative, multi-team, and multidisciplinary program involving investigators from the Departments of Bioengineering, Electrical Engineering, Mechanical Engineering, Medicine, and Pathology at the University of Washington. The objective is to develop and validate a new generation of scanning fiber-optic endoscopes and molecular contrast agents for improving early detection of cancer in luminal organs. The endoscope will be based on advanced micro-electro-mechanical systems (MEMS) technologies, overcoming limitations in current scanning endoscopes by offering fast 2-dimensional raster beam scanning and dynamic focus tracking while maintaining a small diameter (d3 mm). Two micro-scanner technologies with complementary advantages, each aiming to achieve the best performance in its category of technology for endoscope applications, will be developed through this program. A high-speed cantilever waveguide scanner with wide scanning angle will be developed for large-area imaging in fast-changing environment. A micro- mirror scanner with active focus tracking will be developed for high-resolution 3-D imaging. Demonstration of both technologies opens a route to integration of both capabilities in a single endoscope channel in the future. The proposed endoscope will enable real-time 3-D imaging and functional integration of high-resolution optical imaging techniques including optical coherence tomography (OCT) and confocal fluorescence endomicroscopy. The molecular contrast agents will be based upon fluorescently-labeled nanoparticles that display peptide ligands targeting dysplasia and early cancer cells. This proposal aims to advance the current endoscopy technology by overcoming the following challenges: (1) endoscopic beam scanning technology for achieving a uniform, controllable scanning pattern and 3-dismentional imaging capability;(2) maintaining high resolution over various imaging depths;(3) probe miniaturization;(4) the weak intrinsic contrast between normal tissue and pre- or early cancers;and (5) the lack of molecular specificity to early cancers. The targeted spatial resolution (<5 5m) and 3-dimensional imaging capability will significantly improve our currently limited ability for detecting early and pre-cancers. The specific aims of this project are: 1. Develop a miniaturized waveguide cantilever scanner capable of rapid beam scanning (>20 kHz resonant frequency) with wide field of view (>60:) for real-time imaging of large area. 2. Develop deformable MEMS scanning micro-mirror and optical packaging with high resolution (<5 5m) and dynamic focus-tracking (1 mm depth range) for high-quality 3-dimensional imaging. 3. Evaluate the performance of the scanning endoscope for high resolution OCT and confocal fluorescence imaging of normal and early cancer in an in-vivo hamster cheek pouch cancer model. 4. Investigate the feasibility of detecting high-grade dysplasia and intramucosal carcinoma with the scanning probe using fresh human esophagectomy specimens with or without molecular contrast agents. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to develop and validate a new generation of scanning fiber-optic endoscopes and molecular contrast agents for improving early detection of cancer in luminal organs. The endoscope will be based on advanced micro-electro-mechanical systems (MEMS) technologies, overcoming limitations in current scanning endoscopes by offering fast 2-dimensional raster beam scanning and dynamic focus tracking while maintaining a small diameter (d3 mm). The proposed endoscope will enable real-time 3-D imaging and functional integration of high-resolution optical imaging techniques including optical coherence tomography (OCT) and confocal fluorescence endomicroscopy. The molecular contrast agents will be based upon fluorescently-labeled nanoparticles that display peptide ligands targeting dysplasia and early cancer cells. The excellent spatial resolution (<5 5m) and 3-dimensional imaging capability offered by the scanning endoscope and the cancer-targeted nanoparticles providing enhanced contrast will significantly improve our currently limited ability for detecting early and pre-cancers. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1 Continuation Format Page